Margareta Radić Antolic

Inherited Prothrombotic Risk Factors in Children With Stroke, Transient Ischemic Attack, or Migraine

OBJECTIVE. The aim of this study was to investigate the prevalence and possible association of inherited prothrombotic risk factors in children with stroke, transient ischemic attack, or migraine. METHODS. We performed genotypic analysis for factor V G1691A, factor II G20210A, methylenetetrahydrofolate reductase C677T, and 4 common platelet glycoprotein polymorphisms (human platelet alloantigen-1, -2, -3, and -5) in 150 children <18 years of age with established diagnoses of stroke, transient ischemic attack, or migraine. Children were classified into 5 groups, namely, childhood arterial ischemic stroke (N = 33), perinatal arterial ischemic stroke (N = 26), hemorrhagic stroke (N = 20), transient ischemic attack (N = 36), and migraine (N = 35). The control group consisted of 112 children ≤18 years of age from the same geographical region who had no history of neurologic or thromboembolic diseases. RESULTS. Heterozygosity for factor V G1691A was associated with approximately sevenfold increased risk for arterial ischemic stroke, perinatal arterial ischemic stroke, and transient ischemic attack. Increased risk for transient ischemic attack was found in carriers of the human platelet alloantigen-2b allele, human platelet alloantigen-5a/b genotype, and combined human platelet alloantigen-2b and human platelet alloantigen-5b genotype. The presence of the human platelet alloantigen-2b allele was associated with a 2.23-fold increased risk for migraine, whereas carriers of the human platelet alloantigen-3b allele had a lower risk for arterial ischemic stroke than did carriers of the human platelet alloantigen-3a allele. CONCLUSIONS. Factor V G1691A has an important role in susceptibility to arterial ischemic stroke, both in the perinatal/neonatal period and in childhood, as well as transient ischemic attacks. A minor impact of human platelet alloantigen polymorphisms suggests that platelet glycoprotein polymorphisms may increase the risk of transient ischemic attacks and migraine, but this should be confirmed in larger studies.

Inherited prothrombotic risk factors in children with cerebrovascular disorders

Cerebrovascular disorders (CD) are an important cause of mortality and morbidity in children, and an emerging area for clinical research. There is increasing evidence that inherited or acquired prothrombotic disorders may be implicated in the etiology of CD in childhood. We have investigated the prevalence of genetic polymorphisms associated with thrombosis: factor V G1619A (FVL), factor II G20210A (PT), methylenetetrahidropholate reductase C677T (MTHFR), and human platelet antigens (HPA-1, -2, -3 and -5) in 151 children with CD and compared the data with those obtained for the control group (112 children from the same geographical region). Children with CD were classified into 5 groups according to diagnosis based on clinical symptoms, neurological examination, computed tomography and magnetic resonance imaging of the brain: children with arterial ischemic stroke (AIS ; n=36), perinatal arterial ischemic stroke (PAIS ; n=26), transient ischemic attack (TIA ; n=36), migraine (n=35) and intracranial hemorrhage (ICH ; n=18). Similar genotype distributions of all studied polymorphisms were found only between children with ICH and controls. Statistically significant differences between controls and other groups of children with CD were observed for at least one polymorphism: for FVL in children with AIS and TIA (p=0.048), for MTHFR in children with AIS (p=0.036), PAIS (p=0.034) and migraine (p=0.037), for HPA-2 and -5 (p=0.037) in children with TIA. Furthermore, higher frequencies of the HPA-3a allele in children with AIS were found to be statistically significant (p=0.027), as compared to the control group. Obtained results indicate that different polymorphisms are implicated in the etiology of CD in childhood.